Thioformal and acetal derivatives of mercaptopyridine-1-oxide



United States Patent THIOFORMAL AND ACETAL DERIVATIVES OF MERCAPTOPYRIDINE-I OXIDE Jack Rockett, Metuchen, N.J., assignor to Olin Msthieson Chemical Corporation, a corporation of Virginia No Drawing. Application August 26 1958 Serial No. 757,201

9 Claims. (Cl. 268-294.8)

2,932,647 Patented Apr. 12, 1960 non-polar solvent. The hydrohalide salts of this invention can thus be prepared in good yield. Benzene is the preferred medium for this reaction but other inert organic solvents, for example, ethylene dichloride can be used. Any hydroh-alide salt can be prepared but the hydrochlorides and hydrobromides are particularly pre- RAH+CH O +HC1 RACH2Ci+H2O in which R and A are defined before.

This invention relates to a new group of chemical compounds and to processes for their preparation. More Alpha-chloroethers can also be prepared by other particularly, this invention relates to new and useful methods such as the chlorination of an aliphatic ether. monoand ditlioformal and acetal derivatives of 2-rner- For example, alpha,beta,beta'-trichlorodiethylether may captopyridine-oxide. be prepared by the process of Serial No. 330,351, now The compounds of this invention are the bases and the US. Patent No. 2,853,528, issued September 23, 1958. hydrohalides of the bases having the formula Examples of other alpha haloethers which can be used in the process of the present invention include alpha, C H N(- O)S.CI'1R'AR beta-dichlorodiethyl ether, chloromethyl vinyl ether, and alpha,beta,beta'-trichlorodi-isopropyl ether. The re- 111 Whlch A 18 Oxygen Sulfur; R 13 hydrogen, y sultant alpha-chloroethers or thioethers can be employed Carbon halohydlocalbon radical, especlally an alkyl, for the preparation of a mono or dithioformal or acetal alkenyl, alicyclic or aryl radical containing 1 to 18 carbon according to the process herein described. atoms and is y g a lower f l y g P or a halo- Some specific examples of compounds of the present genated lower alkyl group ntaining 1 to 5 carbon invention, suitable reagents for reaction with 2mercapto'- atoms. u pyridinei-oxide to form them, and radicals R and R are The 2-pyr1dyl-1-ox1de radical, C H4N(- 'O)S ill the shown in the following table:

Ident. Reagent A R Product 0 H N 0 SCH OH GHO+HOI 0 i%-ig%rzci?yggestgfil 2s-ngcaptopyridine-l-oxide.

s OH? {p 2 ygid p gig sgmah idicniorormsi.

.9 8 p rviid ysl)--colxclg)c shlliil dithioformsl.

a i-oicnnsomci s r-cunmnls-zz-is r id i-rmie "s l-chiorophenyi dithiO- orma CHN OSCHSCHCH q s s 2-i) %iTi 1;- ti 3 r1 dlthioiormal.

I O {(Si 2-iieI7rid%1)-ggdg)O -eld monothioacetal.

- OHDHOOEOI o H 2- %iid%1)--8:%ri% gaifigvglfiugiglgpformal.

1 oiomcnzocnoionioiw o oiornonh 011,01 S- Q-iJyiId I-I-oXitie) d-z-emowmyi monothiomonochloroacetal.

above formula and the 2-mercaptopyridine-l-oxide have In addition, R can also be beta,beta-dichloroethyl, the structural formulas: isopropyl and n-amyl or other lower alkyl or halogenated 60 lower alkyl group containing 1 to 5 carbon atoms. R

can also be allyl, nand iso-propyl, n-, iso, sec andtertbutyl, 2-ethylhexyl n-dodecyl, n-octadecyl, phenyl 0- BH bromobenzyl and cyclohexyl or other hydrocarbon or 4, I 4, halohydrocarbon radicals containing 1 to 18 carbon 0 0 atoms. -mercantopr 2-uyridyl-l-oxide The compounds of this invention are useful in diluted The compounds of this invention are prepared by the compositions as pesticides. They act as soil fungicides, reaction of, a 2-mercaptopyridine-l-oxide compound in foliage fungicides and in the control of weeds. They are the form of the free acid or a salt with an alpha-haloether able o penetrate the y a ing f f l g nd f rm according'to the following reaction scheme: and thus serve as longer lasting protective fungicides than for example, metal salts of'organic acids, including c5H4N(')O)SM+C1CHR A N SCH M l the heavy metal salts of 2-mercaptopyridine-1-oxide. The "CsHt R c compounds are used advantageously in a proportion of where M is a suitable cation, e.g., a metal or a positive about 15 to 18 percent with any of the dlluents usually radical, for example, hydrogen, sodium, potassium, am employed for the application of foliar fungicides or for monium or substituted ammonium. A, R, R are as deapplication to the soil where they control the activ ty of fined above. This reaction occurs readily and can be soil fungi. The compounds of this nvention are o1ls or carried out in a variety of. reaction media, although crystalline solids and are suitably dispersed on an m ertacetone or dioxane as. the reaction medium is preferredfinely divided solid and employed as a dust. Suitable when a salt ofZ-mercaptopyridinethione is used. solid carriers are clay, talc, bentonite, as well as other Alternatively, the reaction can be carried out by employing 2-mercaptopyridine-l-oxide as a free acid in a carriers known in the art. (See Frear, Chemistry of Insecticides, Fungicides and Herbicides) Microcel 805,

a synthetic calcium silicate is an example of a suitable solid carrier. The compounds may also be applied as a spray in a liquid carrier either as a solution in a solvent or as asuspension ina non-solvent for example, water.

, "When applied as a suspension, suitable wetting agents and "dispersants are incorporated. Marasperse N is a suitable dispersant of the lignosulfonate type. Igepon AP7 8, an ester of sodium isethionate, is a suitable wetting agent. The proportion of dispersant is suitably from about 1 to 3 percent and the wetting agent is suitably from about 2 to 10 percent of the composition. The compounds of this invention may also be admixed with carriers that are themselves active, such as other parasiticides, herbicides I and fertilizers.

. EXAMPLE 1 f S-(Zpyridyl-I-oxid) O-methyl monothioformal cosity. This represented an 87.8 percent yield.

, Analysis.-Calc. for C H NO S: S, 18.72%; N, 8.19%. Found: S, 17.67%; N, 8.32%.

Tests as soil fungicides were carried out by placing discs of agar cultures 5 mm. in diameter of the pathogenic fungi listed in the table below on Petri dish plates of potato dextrose agar containing 10, 100 and 1000 parts per million, respectively, of the chemical being tested The plates were then incubated for 48 hours at 20 C. to give satisfactory growth of the fungi on control plates containing no chemical. The growth of the fungi on the test plates was then observed and noted as 0 for no growth, indicated a kill of the fungi; for grown of the original inoeulum only, indicating a decided depressing etfect of fungus growth but no of the fungus and indicating no inhibition of fungal growth and, therefore, no pronounced depressing eifect of the chemical being tested.

B-(Z-pyridyl-l-oxide) O-methyl monothioiormal, p.p.m. Test Organism I These data show complete control of all of the several fungi tested at 1000 parts per million, nearly complete control at 100 p.p.m. and partial control with as low as l0 p.p.m. of this anti-fungal agent.

EXAMPLE 11 S-(Z-pyridyl-I-oxide) O-n-propyl monothioformal In a flask was placed 300 cc. of dioxane and 44.8 grams (0.3 mole) of sodium salt of Z-mercaptopyridine-l-oxide. 32.6 grams (0.3 mole) of chloromethyl-n-propyl ether were added, dropwise. By intermittent cooling S-(Z-pyridyl-l-oxide) O-n-propy'l monothiotormal, p.p.m. Test Organism I Armillarla melee 0 0 0 Fusarium aolanl 0 0 n F. ozusfiamm t. h copersicl. 0 0 0 Phytop thom cactomm.-. 0 O D 'Pliytophthora cinnamomi. '0 0 O Phytophthora citrophthom. 0 0 0 Pythium apham'dermamm .J 0 0 0 Puthium ultimum 0 0 0 Rhizoctonia solani 0 Sclm'atinia sclerotiorum 0 O 0 Sclerotium rolfsii 0 0 O Streptomyces scabies. 0 0 0 Verticillium albo-ctrum 0 0 0 These data show substantially complete control of all of the several fungi tested with as little as 10 parts per million of this anti-fungal agent.

EXAMPLE III S- (Z-pyridyl-I-)0-2 chlor0ethyl monothiochloroacezal EXAMPLE 1V S-hydroxymelhy I-Z-mercaptopy ridine-I -0xide hydrochloride To a solution of 38.1 grams (0.3 mole) of Z-mercaptopyridine-l-oxide in 250 cc. of ethylene dichloride was added 9.0 grams (0.3 mole) of paraformaldehyde. The

' suspension was" cooled by an ice bath and gaseous hydrogen chloride was passed in for four hours. A heavy precipitate formed which was filtered'and dried. The

' pale ivory colored crystalline material'weighed 56.9

with an ice bath the temperature was kept at 20-30 C.

The flask contents were then heated to 55-60 'C. for

grams, a 98.0 percent yield. The product was S-hydroxymethyl-Z-mereaptopyridine-l-oxide hydrochloride, M.P. 101108 C. v

Analysis.--Calc. for C H C1NO S: Cl, 18.35%; C, H, 4.13%. Found: Cl, 18.32%; C, 36.57%; H,

EXAM PLE V S-(Z-pyridyl-l-axide) O-n-dodecyl monothioformal 0.20 gram mole of the sodium salt of Z-mercaptopyridine-l-oxide was suspended in 500 ml. of acetone. 0.20 gram mole of chloromethyl-n-dodecyl ether was added over a period of 14 minutes at 24-31.C. The mixture was refluxed for 2 hours and filtered hot to remove by-product sodium chloride. Cooling the filtrate yielded 0.175 gram mole of crude n-dodecyl thioformal (88% yield), M.P. 73-77 C. Recrystallization from isopropyl ether yielded 0.117 mole of product, M.P. 78-795 C.

I Analysis .-Sulfur, theory, 9.84%; found, 10.31%.

EXAMPLE vr S-(Zpyridyl-l-oxide) O-ethyl monothioformal Following the procedure of Example V, the sodium salt of Z-mercaptopyridine-l-oxide was treated with chloromethyl ethyl ether. The yield of S-(2-pyridyl-1-oxide) O-ethyl monothioformal was 97 percent of a solid, M.P. 6266 C. It contained 19.0 percent sulfur compared with a theoretical value of 17.3 percent.

EXAMPLE VII S-(Z pyr idyI-I-Oxide) O-isopropyl monothioformal Following the procedure of Example V, the sodium salt of Z-mercaptopyridine-l-oxide was treated with chloromethyl isopropyl ether. The yield of S-(2-pyridy1-1- oxide) O-isopropyl monothioformal was 90 percent of an oil containing 16.5.percent sulfur compared with a theoretical value of 16.1 percent.

EXAMPLE VIII S-(Z-pyridyl-I-oxia'e) O-n-oc tqdecyl monothioformal Following the procedure of Example Y, the sodium salt of 2-mercaptopyridine-1-oxide was treated with chloromethyl n-octadecyl ether. The yield of S-(2- pyridyl-l-oxide) O-n-octadecyl monothioformal was 63 percent of a solid, M.P. 90-93 C. It contained 8.1 percent sulfur which is the theoretical value.

EXAMPLE IX S-(Z-pyridyl-Z-oxide) S-methyl dithioformal Following the procedure of Example V, the sodium salt of 2-mercaptopyridine-1-oxide was treated with chloromethyl methyl sulfide. The yield of S-(Z-pyridyl-loxide) S'-methyl dithioformal was 63 percent of a solid, M.P. 106-107 C. It contained 34.1 percent sulfur compared with a theoretical value of 34.2 percent.

EXAMPLE X S- (Z-pyridyl-I-wtide) O-iso-ocryl monathioformal hydrochloride 6 EXAMPLE XI S-(Z-pyridyZ-l-oxide) 'S-n-prapyl dithioformal hydrochloride Following the procedure of Example X, Z-mercaptopyridine-l-oxide was treated with chloromethyl npropyl sulfide. The resulting S-(2-pyridy1-1-oxide) S-n wherein R is selected from the group consisting of hydrogen and'alkyl, alkenyl, cycloalkyl and monocyclic aryl and chloroand bromo-alkyl, alkenyl, cycloalkyl and monocyclic aryl containing 1 to 18 carbon atoms, R is selected from the group consisting of hydrogen and lower alkyl and chloroand bromo-lower alkyl containing 1 to 5 carbon atoms and A is selected. from the group consisting of S and O.

2. S-(2-pyridyl-1-oxide) O-methyl monothioformal.

3. S-hydroxymethyl-Z-mercaptopyridine-l-oxide hydrochloride.

4. S-(pyridyl-l-oxide) O-dodecyl monothioformal.

5. S-(2-pyridyl-1-oxide) S'-n-propy1 dithioformal hydrochloride.

6. S-(Z-pyridyl-l-oxide) O-Z-chloroethyl monothiomonochloroacetal.

7. A process for the preparation of a compound according to claim 1 which comprises reacting a 2-mercaptopyridine-l-oxide compound with a compound selected from the group consisting of alpha-halothioether and alpha-haloether.

8. A process for the preparation of a compound according to claim 1 which comprises reacting a salt of Z-mercaptopyridine-l-oxide with a compound selected from the group consisting of alpha-chlorothioether and alpha-chloroether.

9. A process for the preparation of a compound according to claim 1 which comprises reacting Z-mercaptopyridine-l-oxide with a compound selected from the group consisting of alpha-chlorothioether and alpha-chloroether V and recovering the hydrochloride product.

References Cited in the file of this patent UNITED STATES PATENTS UNITED STATES PATENT OFFICE CERTIFICATE OF CORRECTION April 12, 1960 Patent No a 2,932,647

Jack Rockett It is hereby certified that error appears in the-printed specification of the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

I Column 2, line 64 for 18" read 80 column 6,, line 28 for "-(pyridyl-L-oxide) read (2-pyridyllox1d e) "a Signed and sealed this 27th day of September 1960 (SEAL) Attest;

KARL Ho AXLINE ROBERT C. WATSON Commissioner of Patents Attesting Officer 

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF FREE BASES AND HYDROHALIDES OF FREE BASES HAVING THE FORMULA: 